Enhanced US/CT/MR imaging of integrin αvβ3 for liver fibrosis staging in rat

Xueyao Tang; Xueyao Tang; Xuan Li; Xuan Li; Mingxing Li; Xiaoling Zhong; Wenguang Fu; Wenguang Fu; Meng Ao; Jiqing Xuan

doi:10.3389/fchem.2022.996116

Frontiers in Chemistry (Oct 2022)

Enhanced US/CT/MR imaging of integrin αvβ3 for liver fibrosis staging in rat

Xueyao Tang,
Xueyao Tang,
Xuan Li,
Xuan Li,
Mingxing Li,
Xiaoling Zhong,
Wenguang Fu,
Wenguang Fu,
Meng Ao,
Jiqing Xuan

Affiliations

Xueyao Tang: Department of Ultrasound, The Affiliated Hospital of Southwest Medical University, Luzhou, China
Xueyao Tang: Department of Ultrasound, The Third People’s Hospital of Chengdu, Clinical College of Southwest Jiao Tong University, The Second Affiliated Chengdu Hospital of Chongqing Medical University, Chengdu, China
Xuan Li: Department of Ultrasound, The Affiliated Hospital of Southwest Medical University, Luzhou, China
Xuan Li: Department of Ultrasound, Sichuan Provincial People’s Hospital, Chengdu, China
Mingxing Li: Department of Ultrasound, The Affiliated Hospital of Southwest Medical University, Luzhou, China
Xiaoling Zhong: Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
Wenguang Fu: Academician (Expert) Workstation of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, China
Wenguang Fu: Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
Meng Ao: Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, China
Jiqing Xuan: Department of Ultrasound, The Affiliated Hospital of Southwest Medical University, Luzhou, China

DOI: https://doi.org/10.3389/fchem.2022.996116
Journal volume & issue: Vol. 10

Abstract

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Liver fibrosis is a global health challenge with high morbidity and mortality rates, and diagnostic sensitivity of liver fibrosis tests can be increased using multimodal molecular agents. We designed cyclic arginine-glycine-aspartic acid (cRGD)-modified nanoparticles (NPs) using ultrasound (US)/computed tomography (CT)/magnetic resonance (MR) triple-modality imaging to evaluate liver fibrosis stages. In vitro and in vivo studies were conducted using primary hepatic stellate cells (HSCs) and a rat model of liver fibrosis induced by carbon tetrachloride (CCl4). Our results showed cRGD-poly(lactic-co-glycolic acid)-Fe3O4-perfluorocarbon bromide (cRGD-PLGA-Fe3O4-PFOB) NPs were preferentially internalised by activated HSCs (aHSCs). The main cell types expressing integrin αvβ3 during liver fibrogenesis were the aHSCs. The protein levels of αv and β3 expressed on aHSCs increased with the progression of liver fibrosis. After intravenous injection of cRGD-PLGA-Fe3O4-PFOB NPs, the echo intensity (EI) values, CT values, and T2 values of liver parenchyma correlated well with liver fibrosis severity. cRGD-PLGA-Fe3O4-PFOB NPs as multifunction contrast agents showed great potential to reflect the degree of HSC activation and distinguish among different liver fibrotic stages. The ligand-directed and integrin αvβ3-mediated accumulation provides active and passive targeting capabilities, permitting the targeted multimodal imaging of cRGD-PLGA-Fe3O4-PFOB NPs, which delivers accurate non-invasive diagnosis and real-time monitoring of liver fibrosis development.

Published in Frontiers in Chemistry

ISSN: 2296-2646 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Chemistry
Website: http://journal.frontiersin.org/journal/chemistry

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